Alteration of gap junctions and connexins in the right atrial appendage during cardiopulmonary bypass

OBJECTIVES: We investigated the influence of cardiopulmonary bypass on cardiomyocyte gap junctions and connexins. METHODS: Samples were collected at intervals during operation from the right atrial appendage in 21 patients (mean [+/- SD] age 55 +/- 21 years). Immunodetection of connexins was conducted by Western blotting and confocal microscopy with parallel electron microscopic examination of gap junctions. RESULTS: Downregulation of connexin 43 during the course of operation occurred in more than half of the patients. The mean densitometric value of connexin 43 decreased by 23%, with samples from patients with coronary artery disease showing a greater reduction than seen in those from patients with other diseases (31% +/- 22% vs 10% +/- 24%, P =.04). Such alterations were confirmed by confocal microscopy, which also demonstrated reduced connexin 45 immunolabeling in most patients. Electron microscopy revealed a reduction in the dimensions of cell membrane-located gap junctions and more frequent intracytoplasmic gap junctional membrane in samples from later time points (P =.04). CONCLUSIONS: Downregulation of connexins accompanied by a reduction in gap junctions is common in the cardiomyocytes of the right atrial appendage during cardiopulmonary bypass. The association of a marked reduction in connexin 43 with coronary artery disease may imply inadequate intraoperative cardiac protection in patients with this disease.     

Preconditioning with hyperbaric oxygen and hyperoxia induces tolerance against spinal cord ischemia in rabbits

BACKGROUND: The aim of this study was to determine if the ischemic tolerance could be induced in the spinal cord by pretreatment with hyperbaric oxygen (HBO) and what components of HBO (hyperoxia, hyperbaricity, and combination of these two) were critical in the induction of tolerance against ischemic injury. METHODS: In experiment 1, 21 rabbits were randomly assigned to one of three groups (n = 7 each): animals in the control group received no HBO before spinal cord ischemia; animals in the HBO-1 and HBO-2 groups received HBO (2.5 atmosphere absolute [ATA], 100% O2) pretreatment 1 h/day for 3 and 5 days before ischemia, respectively. In experiment 2, 48 rabbits were randomly assigned to one of four groups (n = 12 each): the control group received no HBO (21% O2, 1 ATA, 1 h/day, 5 days) before spinal cord ischemia; the HB group received 1-h treatment in 21% O2 at 2.5 ATA each day for 5 days; the HO group received 1-h treatment in 100% oxygen at 1 ATA each day for 5 days; and the HBO group received HBO (2.5 ATA, 100% O2) treatment 1 h/day for 5 days. Twenty-four hours after the last treatment, spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min. Forty-eight hours after reperfusion, hind-limb motor function and histopathology of the spinal cord were examined in a blinded fashion. RESULTS: In experiment 1, the neurologic outcome in the HBO-2 group was better than that of the control group (P = 0.004). The number of normal neurons in the anterior spinal cord in the HBO-2 group was more than that of the control group (P = 0.021). In experiment 2, the neurologic and histopathologic outcomes in the HBO group were better than that of the control group (P < 0.01). The histopathologic outcome in the HO group was better than that in the control group (P < 0.05). CONCLUSIONS: Serial exposure to high oxygen tension induced ischemic tolerance in spinal cord of rabbits. Simple hyperbaricity (2.5 ATA, 21% O2) did not induce ischemic tolerance.     

Aortic wall alterations after use of gelatin-resorcinol-formalin glue

We report the case of a patient who underwent reoperation 8 years after aortic valve replacement because of aneurysmal dilatation of the aortic root. During the initial intervention, gelatin-resorcinol-formalin glue had been applied on the outside of the aortic root. Perioperative examination revealed a necrotic appearance of the right coronary sinus, with contained ruptures at two different sites. Histologic analysis showed major destruction of the aortic root media, leading to vascular wall thinning and rupture. The use of gelatin-resorcinolformalin glue may expose patients to major alterations of the aortic wall.     

High frequency loss of heterozygosity on the long arms of chromosomes 13 and 14 in nasopharyngeal carcinoma in Southern China

目的：分析鼻咽癌（NPC）13号染色体长臂（13q）和14号染色体长臂（14q）上21个位点的等位基因杂合子丢失（LOH）,并分析这些位点的LOH与NPC临床病理及EBV感染的关系。方法：用聚合酶链反应（PCR）为基础的微卫星多态性分析技术结合基因扫描和基因绘图技术对60例NPC进行LOH分析。结果：13q染色体发生一个或多个位点LOH频率为78％,高频率LOH（大于30％）位点集中于13q12.3-q14.3和13q32附近。14q染色体发生至少一个位点LOH的频率为80％,高频率丢失位点集中于14q11-q13、1q421-q24和14q32附近。13q31-q32位点的LOH与低滴度血清EBV EA/IgA有关;14q染色体的LOH与NPC细胞的分化差有关。结论：华南地区鼻咽癌在13q和14q染色体发生高频率的LOH,这些缺失区可能存在多个在NPC发生发展过程中起重要作用的肿瘤抑制基因。     

血液透析病人外周血单核细胞糖基化终产物受体的表达及其与细胞因子水平的关系

目的　探讨慢性肾功能衰竭长期血液透析病人外周血单核细胞表面晚期糖基化终产物(AGE)受体的表达及其与循环肿瘤坏死因子α(TNFα)和白细胞介素 1β(IL 1β)水平之间的关系 ,以及血透病人循环中高水平促炎症细胞因子的发生机制。方法　选择慢性肾功能衰竭病人 5 9例 (其中非透析组 2 2例 ,维持性血透组 37例 )和正常人 30例 ,观察单核细胞表面AGE结合蛋白的数量和亲和力 ,检测单核细胞表面AGE受体 (RAGE)的表达及单核细胞培养上清中的TNFα和IL 1β的水平。 结果　血透病人单核细胞与12 5I AGE 白蛋白的特异性结合率 (41 4fmol/ 10 5细胞± 2 2fmol/ 10 5细胞 )较正常人 (31 6fmol/ 10 5细胞± 4 1fmol/ 10 5细胞 ,P <0 0 5 )明显升高 ,细胞表面AGE结合蛋白的数目(2 4 2± 0 2 1× 10 5/细胞 )高于正常人 (1 74± 0 2 9× 10 5/细胞 ,P <0 0 5 ) ,但亲和常数 (Kd)与正常人单核细胞相比无明显差异 ;血透病人单核细胞表面RAGE表达亦高于正常人 ;在相同剂量AGE 白蛋白刺激下 ,血透病人单核细胞分泌的TNFα和IL 1β水平较正常人明显升高 ,这种升高作用可被抗RAGE抗体所阻断 ;单核细胞AGE结合蛋白表达上调的血透病人 ,其循环TNFα和IL 1β水平亦显著升高。结论　血透病人单核细胞AGE受体表达上调 ,在     

Double partial monosomies (10p- and Xp-) in a female baby with choanal atresia

Chromosomal abnormalities involving double partial monosomies are very rare. A female infant with non-mosaic monosomy 10p13-->10pter along with monosomy Xp11.4-->Xpter which arose de novo is described. The clinical manifestations of this patient included microcephaly, mild synophrys, short and down-slanted palpebral fissures, ptosis of the left eye, long eyelashes, a depressed nasal bridge, dysplastic ears, micrognathia, a short neck. sensorineural hearing impairment, and severe growth retardation. Left choanal atresia and laryngomalacia were detected by flexible fibroscopy. No signs of hypoparathyroidism or defective cellular immunity could be found. Fluorescence in situ hybridization (FISH) with whole-chromosome painting probes for chromosomes 10 and X was performed, which excluded the possibility of cryptic translocations of the involved chromosome segments. No submicroscopic chromosome 22q11 deletion could be found by FISH. Thus this very rare coexistence of double independent partial monosomies was confirmed. There are no previous reports of such concurrent double partial monosomies.     

Radioiodinated styrylbenzene derivatives as potential SPECT imaging agents for amyloid plaque detection in Alzheimer's disease

Development of probes for β-amyloid (Aβ) plaques, a critical factor associated with Alzheimer’s disease (AD), provides important tools for studying their role in AD. Previously, we reported [¹²⁵I]IMSB and [¹²⁵I]ISB as excellent probes for Aβ plaque labeling. Despite their exquisite in vitro binding characteristics, low brain uptakes (likely due to two ionizable carboxylic acid groups) limited their potential as in vivo imaging agents. To improve brain penetration, we have successfully prepared a neutral radioiodinated probe [¹²⁵I]3. The improved probe displayed good binding affinity for Aβ aggregates (K_i=2.0 ± 0.2 using Aβ40 aggregates). In addition, the brominated counterpart displayed fluorescent-staining properties of Aβ plaques in postmortem AD brain sections similar to BSB, a fluoroscent probe reported previously. [¹²⁵I]3 gave excellent plaque labeling by film autoradiography of AD brain sections. Unlike [¹²⁵I]IMSB (which preferentially detects Aβ40 plaques), the improved radioioinated probe, [¹²⁵I]3, can readily detect plaques containing aggregates of both Aβ40 and Aβ42. The initial brain uptake of [¹²⁵I]3 in normal mice at 2 min p.i. was moderate (0.18% ID) and displayed a very slow washout from the brain (0.11 %.ID at 4 h p.i). Taken together, these data suggest that [¹²⁵I]3 is useful for in vitro plaque detection, it may not be suitable for in vivo monitoring of Aβ progression and deposition.     

Her-2/neu expression and gene amplification in gastrinomas: correlations with tumor biology,growth, and aggressiveness

A proportion of gastrointestinal neuroendocrine tumors are aggressive; however, little is known of molecular determinants of their growth, and molecular studies have identified no useful prognostic factors. Overexpression of HER-2/neu is common in some nonendocrine tumors, frequently correlates with increased tumor aggressiveness, and can be used as a basis of treatment with trastuzumab. Little is known of its expression in malignant pancreatic endocrine tumors. In the present study HER-2/neu gene amplification and expression was determined in 43 gastrinomas from different patients. Results were correlated with clinical, laboratory, and tumor characteristics including tumor growth. HER-2/neu gene amplification was assessed by differential PCR, mRNA levels assessed by quantitative PCR, and protein by immunohistochemistry. Fourteen percent of patients had HER-2/neu gene amplification in tumors compared with levels in their WBCs. HER-2/neu mRNA varied over a 700-fold range. However, only 3% exceeded levels seen in normal pancreas, and immunohistochemistry did not show protein overexpression in any tumor (n = 10). HER-2/neu mRNA levels were significantly higher (P = 0.032) in tumors associated with liver metastases but not with tumor location or size. These results show that HER-2/neu amplification/overexpression does not seem to play a role in the molecular pathogenesis of most gastrinomas, as suggested in a previous study involving small numbers of cases. However, mild gene amplification occurs in a subset, and overexpression is associated with aggressiveness. Therefore, HER-2/neu levels could have prognostic significance as well as identify a patient subset with gastrinomas who might benefit from trastuzumab treatment.     

乳腺癌淋巴道转移潜能与癌细胞中钙粘素及金属蛋白酶的关系

背景及目的:目前尚缺少有效评价乳腺癌淋巴道转移潜能的理想指标。本研究旨在通过检测上皮性钙粘素(E-cadherin,E-Cad)、神经性钙粘素(N-cadherin,N-Cad)和基质金属蛋白酶-9(matrixmetalloproteinase-9,MMP-9)基因产物在乳腺癌组织中表达的情况来探讨它们与乳腺癌浸润和转移的关系。方法:采用免疫组织化学SP方法检测E-Cad、N-Cad和MMP-9在72例乳腺浸润癌(其中淋巴结转移39例,无淋巴结转移33例)中的表达,并用多因素Cox比例风险模型分析患者的预后。结果:E-Cad表达在淋巴结转移组和无淋巴结转移组乳腺癌肿瘤细胞中的平均秩次分别为29.19,45.14,两组差异显著(P<0.001),E-Cad表达与乳腺癌转移呈负相关;N-Cad和MMP-9在淋巴结转移组乳腺癌细胞中的平均秩次分别为40.04和42.97;在无淋巴结转移组乳腺癌肿瘤细胞中的平均秩次分别为32.32和28.85。二者在淋巴结转移组与无淋巴结转移组的表达均具有显著性差异(P<0.05),与乳腺癌淋巴结转移呈正相关。E-Cad高表达者生存时间长。结论:乳腺癌的淋巴道转移与E-Cad、N-Cad和MMP-9的表达具有显著相关性,检测这几种蛋白表达将有助于判断乳腺癌的转移潜能及预后。